1. Field
This invention relates to multiphoton radioisotope detectors with ultralow background. These detectors can quantify coincident gamma and X-ray emissions from electron capture (EC) isotopes, combining coincident counting and other background rejection measures to achieve extraordinary sensitivity.
2. Background Information
One basis of classifying detectors is according to the nature of the read-out process. In one class of detectors (photographic emulsions, phosphor imagers) the signal is integrated over a long time period (typically much longer than minutes) and only subsequently quantitated. In a second class of detectors, events are registered and analyzed on a particle-by-particle basis. This class of detectors includes gas detectors, liquid noble gas detectors, scintillators, and semiconducting detectors.
Another basis for detector classification relates to operating conditions; for biomedical applications, detectors operating at low temperature (e.g., liquid noble gas detectors, germanium detectors) and detectors requiring high pressure (pressurized gas detectors) are not as popular as detectors which operate at room temperature and ambient pressure.
A third classification approach relates to background and detector sensitivity. Detectors may be classified as (a) ultralow background detectors (ULBD) with radioactive background of less than 0.1 count per hour (&lt;0.1 cph); (b) very low background detectors with radioactive background of less than 1 cph (&lt;1 cph); and (c) low background detectors with radioactive background less than 1 count per minute (&lt;1 cpm). F. T. Avignone et al., Phys. Rev. C34 (1986) 666; R. L. Brodzinski et al., NIM A254 (1987) 472; R. L. Brodzinski et al., J. of Radioanalytical and Nuclear Chemistry, 124 (1988) 513.
There are few operational ULBDs, which are typically located in large underground laboratories, and use large (multikilogram) high purity Germanium (Ge) detectors. Such detectors reduce radioactive background to about one count per day at hard X-ray energies (20-50 keV), thus allowing the detection of a solitary radioactive atom. These facilities, however, are very expensive; they are remote, and their underground location is incompatible with analytical use.
Conventional very low radioactive background detectors are very heavy, typically using over a ton of lead shielding. Conventional low background systems are used for research, and biomedical and environmental diagnostic applications. They typically use a semiconducting Ge detector with a scintillator anti-coincidence shield. However, Ge detectors have to be operated in liquid nitrogen, which severely limits their usefulness particularly when portability is desired, and they are expensive, particularly for detectors of higher energy gammas, which require 2 kg Ge detectors.
Other conventional radiation detectors have background larger than one count per minute. Gas detectors typically have an energy resolution of 10% for hard-X-rays, at 30 keV. X-ray gas detectors with heavy passive shields typically have 20-30 cpm background. They have low stopping power and require large size gas purification systems, and so have been replaced by scintillation counters in many applications. Conventional large gas detectors such as multiwire proportional chamber (MWPC) type detectors provide high spatial resolution, but require expensive multichannel electronics and have high background. Conventional drift gas chambers with fewer wires are preferred in ultralow background applications, but have poor spatial resolution in both directions for low energy deposition, e.g., when X-rays are stopped.
Scintillators are the most popular detectors for quantitation of hard X-rays and gamma-rays. There are three classes of scintillators, namely: liquid scintillators, plastic scintillators, and inorganic crystal scintillators, e.g., NaI(Tl), CsI(Tl), CaF.sub.2 (Eu). Good energy resolution is a goal in low background detectors achieved by selected scintillator/photosensor combinations. Among the scintillators NaI(Tl) and CsI(Tl) produce the best light yield, while among photosensors, photomultiplier tubes (PMT's) permit counting of single photoelectrons. The NaI(Tl)/PMT combination has been very popular in biomedical instrumentation.
Conventional particle/radiation detectors based on scintillator/PMT combinations can detect radioisotopes with characteristic gamma photons from about 30 keV (I.sup.125) to about 1 MeV. These detectors usually optimize detection efficiency rather then minimize radioactive background. Multichannel analyzers (MCAs) are used to perform pulse height analysis. In detectors dedicated to high count-rate studies, the MCA is often replaced by hardware implemented upper/lower level thresholds and counters to diminish detector dead time.
In scintillation counting, liquid or solid scintillators are used to convert the beta or gamma decay energy into a pulse of visible photons, and the total photon number, which is proportional to the original particle energy, is analyzed. Disadvantages of such systems include: weight and bulk due to necessary shielding; mediocre energy resolution which limits the number of co-resident labels that can distinguished; and background levels on the order of twenty counts per minute (20 cpm). Also, some scintillators, e.g., NaI(Tl), are highly hydroscopic and thus require an appropriate housing.
Typically, a well scintillation detector (a single crystal with a hole for a sample) is used to detect and quantify low energy isotopes. To maximize the detection efficiency (DE) for higher energies, it usually has a rather large volume with typical energy resolutions of dE/E(FWHM) of 30% and 9% at 30 keV and 511 keV, respectively. Even with thick (3-4 inches of lead) shielding, the background count rate at low energies is on the order of 20-40 of counts per minute. The background is produced by cosmic rays entering the large detector volume, ambient radiation and internal contamination, for example. The cosmic rays produce low-energy background counts in two major ways: through direct excitation of atoms in the detector which then emit characteristic X-rays, and by saturating the electronics which produces spurious pulses. High-energy gamma photons from the environment (mostly K.sup.40, Tl.sup.208, Bi.sup.2O4, a radon daughter in the air, and man-made contaminants) penetrate the shielding and produce secondary low-energy gamma/X-rays. Scintillators typically have radioactive contamination from K.sup.40 actinides. Even with their high detection efficiency of 70-90%, the high background results in a minimum required input radioactivity of tens of nanoCuries (nCi) per sample.
In a typical single sample detector which uses a "well" geometry, a relatively small sample, say 1 ml or less, is placed into a cylindrical "well" NaI(Tl) scintillator. Typically, the crystal is large, &gt;100 cm.sup.3, and a single PMT is used to collect the light. This geometry is used when high DE (&gt;80%) is required, and has an additional advantage that the DE is largely independent of the sample shape and the precision with which it is placed in the detector. A significant disadvantage of the well geometry is that only a fraction of the total scintillation light is collected, which degrades the energy resolution. Thus, large well detectors are excellent for quantitation of high energy photons (E&gt;100 keV), but their performance deteriorates for low energies (E&lt;50 keV).
Another frequently used geometry is a flat scintillator coupled to a single PMT. Unfortunately, this geometry leads to serious problems with calibration and requires very high precision in sample placement. Also, absorption artifacts are typically difficult to account for in this geometry, and detection efficiency is reduced due to geometric considerations.
Iodine isotope labels are extensively employed in immunoassays utilized in clinical medicine and in basic research in biochemistry, nuclear medicine, and molecular and cellular biology. Iodine is readily adducted at double covalent bonds of organic molecules, including nucleic acids, carbohydrates and proteins. Conventional detectors with backgrounds in the 10-40 counts per minute (cpm) range require use of isotopes with relatively large activity. Competitive radioassays such as radioimmunoassay (RIA) have many advantages (very high sensitivity, large number of well-understood/calibrated kits, and generally years of accumulated know-how) and are widely used in biomedical applications. However, RIA is increasingly being replaced by radioisotope-free techniques such as fluoroimmunoassay and enzymatic immunoassay, due to significant hazardous material handling and disposal problems.
Detectors for counting single gamma photons are designed for broad applicability to permit measurements of large families of gamma emitters with energies ranging from a few tens of keV to a few MeV. In these devices, multi-channel analyzer (MCA) electronic systems distinguishing energy pulse heights generally serve to discriminate the energies of emissions for the plurality of source isotopes. Counting efficiency is maximized to provide the highest sample throughput. The potential of lower efficiency techniques has been generally overlooked.
Hardware implemented coincidence counting is used in a detector for positron-gamma (pg) emitters disclosed in U.S. Pat. No. 5,083,026. Within 10 nanoseconds after the coincident emission of a positron and a gamma, the positron annihilates the electron producing two back-to-back gamma photons with energies of 511 keV. Multiple scintillation detectors are used to register the three coincident high energy (E.gtoreq.250 keV) gammas, and events lacking this triple gamma signature are rejected. These instruments have serious limitations, in particular the type of isotopes that may be used and the large mass and high cost of the scintillator crystals.
Some gamma photon emitting isotopes (coincident gamma and x-ray emitters, or "CGX" emitters) acquire their excited nuclear state through an electron capture (EC) from the S shell (lowest energy state). An unstable S shell vacancy and an unstable excited nuclear state result. In some cases, there is a prompt gamma photon emission from the nucleus (within less than a microsecond). Such prompt emissions may be referred to as proceeding through the "CGX" channel. The S shell vacancy may be filled by the dropping of an outer shell electron with concomitant emission of an X-ray photon or through a cascade of low energy transitions (typically below 10 keV) which progressively restructures the electron shells. However, these special characteristics of CGX emitters have not previously been employed in radioisotope detectors.
Simultaneous counting of individual and coincident gamma and x-rays is taught in Oesterlin et al., U.S. Pat. No. 4,005,292, Horrocks et al., U.S. Pat. No. 4,016,418, and Coffey, U.S. Pat. No. 3,974,088. However, these are all limited to high radioactivity applications.
Fymat et al. (U.S. Pat. No. 4,682,604) describes a tomographic probe for the detection of isotopes incorporated into selected human organs, using an array of unshielded detectors. An isotope source emitting two photons of different energy is used to remove uncertainty in the tissue attenuation coefficient due to Compton scattering and photoelectric scattering. By comparing the attenuation at two different energies, one can calculate the difference in path length traversed by the two photons. However, coincidence is not used to reject background in low activity sources, as the detected activity ranges from 2,000 to 10,000 cps, and the isotope activity is greater than a microCurie.